Pediatric Parenteral Nutrition

Pediatric Parenteral Nutrition : 

Pediatric Parenteral Nutrition Kathleen Gura Pharm.D. Department of Pharmacy Division of Gastroenterology and Nutrition Children’s Hospital Boston Kathleen.Gura@childrens.harvard.edu

Learning Objectives : 

Learning Objectives List and discuss the common complications of PN Identify the indications and monitoring parameters for an infant receiving PN Explain why neonates and infants require a specialized amino acid solution when receiving PN

Goals of Nutrition Support : 

Goals of Nutrition Support Provide nutrition support consistent with: patient’s medical condition nutritional status available route of nutrient administration Prevent deficiencies Provide adequate nutrition to meet metabolic needs Avoid complications Improve patient outcomes

Assessment of Nutritional Status : 

Assessment of Nutritional Status Growth curves - Babson - Lubchenco Intake/output Weight Anthropometric measurements Visceral proteins 24 hour urine studies immune function tests

Dietary History : 

Dietary History Usual nutrition intake and dietary habits anorexia, vitamins and minerals, food allergies Any recent involuntary weight changes Dentition Food intolerance/aversions/allergies Cultural dietary restrictions

Medical History : 

Medical History Underlying disease states digestive disorders, hyperlipidemia, infections chronic blood loss End-organ effects weight changes, energy level, fatigue, nausea fistulas, open wounds trauma, recent surgery Miscellaneous medications, genetic background, alcohol

Physical Examination of Patient : 

Physical Examination of Patient Overall body appearance thin/overweight, dehydrated/edematous Skin and muscle appearance scaly skin, decubitus ulcers, poorly healing wounds, brittle, sparse hair End organ damage Ascites, Jaundice Encephalopathy Hepatomegaly

Anthropometrics : 

Anthropometrics Body weight: includes all of the following: skeletal mass body fat energy-utilizing component (lean body mass) Most helpful when repeated over time Consider alterations in body weight fluid status (dehydration vs. edematous) Usual body wt vs admit wt vs current wt consider wound dressings, casts, recent amputations when evaluating weight changes

Anthropometrics : 

Anthropometrics Length before 36 months – measure recumbent length >36 months, measure standing height Weight useful in evaluating in proportion to height distinguishing wasting vs short stature Head circumference influenced by nutritional status until 36 months of age last anthropometric parameter to be affected by nutritional state < 5th percentile: chronic undernutrition during fetal development or early childhood After 40 weeks PCA use NCHS curves using CGA

Head circumference : 

Head circumference

Growth Charts : 

Growth Charts Available for males and females Birth to 36 months 2 years 18 years Indicate appropriate growth for age -weight, height, wt/ht for age -head circumference for children < 36 months of age 50th percentile standard for age > 90th percentile deficiency excess < 10th percentile represents deficiency Preemies should have their own charts or must be age corrected if standard infant chart used

Daily Monitoring Parameters : 

Daily Monitoring Parameters Daily weights Vital signs Input/Output Nutritional intake Residuals Rate changes Electrolytes Glucose CBC Signs of infection

Normal Growth : 

Normal Growth Full term infants - require 100-135 kcal/kg/day - initial weight gain 25-30 grams/day - by DOL 14: regain birth weight - 3 months: gain 1 pound/month - 4-6 months: double birth weight - 1 year: triple birth weight, length increases by 50% 2 years – puberty: gain 2-3 kg/year, grow 5-8 cm/ year

Parenteral Nutrition : 

Parenteral Nutrition

What’s Different : 

What’s Different Need to maintain current weight as well as continue to grow Time lag to initiation of therapy is less -less fat reserves to sustain them -preemie: start within first 1-3 days of life -infants: after 3-5 days of suboptimal intake -older children: after 3-7 days of suboptimal intake

When PN can be life supporting : 

When PN can be life supporting functional short gut prematurity inflammatory lesions ileus anatomic short gut severe anorexia/hypermetabolism cancer burns

Contraindications to PN : 

Contraindications to PN anticipated duration of therapy <3 days unless severe malnutrition present functional GI tract inability to obtain venous access prognosis doesn’t warrant aggressive nutrition support

Indications for PN Use : 

Indications for PN Use Typically initiated within first 72 hours of life non functional GI tract Abnormal nutritional status (<5th percentile weight for age) Low birth weight (<2.5kg) NPO > 3-5 days (start within 24-48 hrs of birth) Severe catabolic stress

Venous Access : 

Venous Access central umbilical peripheral femoral

Central Venous Access : 

Central Venous Access

Umbilical Lines : 

Umbilical Lines

Fluid Requirements : 

Fluid Requirements 24 weeks GA 90% of infant’s total body mass is water By 40 weeks GA, decreases to 40% as extracellular compartment decreases and the intracellular compartment increases Insensible fluid losses indirectly proportional to gestational age Most infants advance through several stages of fluid requirements until they reach goal status

Fluid Requirements : 

Fluid Requirements **GIVE MAINTENANCE FLUIDS , THEN ADEQUATE CALORIES** 0-10 kg: 100 mL/kg/day 11-20 kg: 1000 mL + 50 mL/kg for each kg above 10 kg >20 kg: 1500 mL + 20 mL/kg for each kg above 20 kg

Fluid RequirementsInfants tend to have greater body surface areas than older children and adults, thus require more fluid : 

Fluid RequirementsInfants tend to have greater body surface areas than older children and adults, thus require more fluid increase fluid needs: -radiant warmers -phototherapy (“bili lights”) -some incubators -skin breakdown -omphalocele -congenital skin defects -cold stress/increased activity -RDS -hyperventilation decrease fluid requirements: -heat shields -double walled incubators -highly humidified environments

Caloric Requirements : 

Caloric Requirements Vary dramatically based on age of child -preemies >older children due to “catch up”growth Approximately 150% of basal metabolic rate varies with clinical state -congenital heart disease -bronchopulmonary dysplasia (BPD) -ventilated, use of paralytic agents varies with intensity of condition NO difference in requirements based upon gender until adolescence

Caloric Requirements(kcal/kg/day) : 

Caloric Requirements(kcal/kg/day) Preterm 120 -150 < 6 months 90 - 120 6 - 12 months 80 – 100 In general, caloric requirements for PN are less than EN due to decreased activity and lack of fecal losses. PN requirements ~10-25% lower than EN - protein calories included

Components of PN : 

Components of PN Macronutrients - Dextrose - Protein (amino acids) - Fat Micronutrients - Electrolytes - Minerals - Vitamins - Trace elements

Components of PN: Amino Acids : 

Components of PN: Amino Acids crystalline form essential most non essential AA 4 cal /gm function: - to maintain or rebuild lean body mass - support immune function 2% OK for PIV; central line 3-4%

Protein : 

Protein Plasma amino acid profiles of neonates vary with gestational age neonates have have immature metabolic systems -lack hepatic enzymes needed to convert methionine to cysteine that is converted to taurine (conditionally essential amino acids) neonates given “adult/standard” amino acid solutions tend to have abnormal amino acid profiles and poor growth

Conversion of Methionine toCysteine and Taurine : 

Conversion of Methionine toCysteine and Taurine

Protein Requirements (gm/kg/day) : 

Protein Requirements (gm/kg/day) Extremely LBW VLBW neonate Term infant Initial 0.5-1 Advance daily 0.5-1 Goal: 2.5 -3.5 Initial: 1-1.5 Advance daily 0.5-1 Goal: 2.5 -3 Initial 1-2 Advance daily 1 Goal: 2.5

Pediatric Amino Acid SolutionsAminosyn® PF (Abbott) TrophAmine®(BBraun)Premasol® (Baxter) : 

Pediatric Amino Acid SolutionsAminosyn® PF (Abbott) TrophAmine®(BBraun)Premasol® (Baxter) designed to match plasma amino acid profiles of healthy breast fed infants contain less methionine/glycine/phenylalanine contain conditionally essential amino acids -taurine, glutamate, aspartate cysteine added at time of PN preparation due to stability issues -dose: 40 mg per each gram amino acid -increases chloride load of solution (caution metabolic acidosis) -improves calcium/phos solubility by decreasing pH -improves nitrogen retention

Components of PN: Dextrose : 

Components of PN: Dextrose cheap, stable, easily stored 3.4 cal/gm fuel source for CNS, RBC, renal medulla 10 % O.K. for PIV osm > 900 requires CVL

Carbohydrates (Dextrose) : 

Carbohydrates (Dextrose) Total amount should not exceed daily amount the body can utilize Don’t exceed body’s max. oxidative rate Infants require more CHO than adults and older children due to increased energy needs initial concentration: 10% exception: neonates (can’t tolerate large dextrose load due to decreased insulin production) If max. oxidative rate exceeded -fatty liver -insulin resistance -hyperglycemia

Carbohydrate Requirements : 

Carbohydrate Requirements neonate: preterm: 5-7 mg/kg/minute term: 6-9 mg/kg/minute advance slowly 1-3mg/kg/day until goal of 12 mg/kg/minute reached infants: initial: 7 mg/kg/minute advance to goal of 10-18mg/kg/minute adolescents initial: 3-5 mg/kg/minute advance to goal of 5-7 mg/kg/minute

Intravenous Fat Emulsions : 

Intravenous Fat Emulsions Preemies at greater risk for essential fatty acid deficiency (EFAD) due to limited fat stores S &S of EFAD -impaired wound healing -dry skin and hair -poor growth Prevent by providing 2-5% of total calories as fat

E.F.A. Deficiency : 

E.F.A. Deficiency

Components of PNIV Fat Emulsion : 

Components of PNIV Fat Emulsion 2nd source of non protein calories 9 calories/gram U.S. products mostly omega 6 fatty acids use: hormone & prostaglandin synthesis structural component of cell membranes role in parenteral nutrition -prevent essential fatty acid deficiency -provide calorically dense source of calories -minimize insulin requirements by decreasing total CHO calories

Components of PN IV Fat Emulsion : 

Components of PN IV Fat Emulsion soybean & safflower oil LCT’s egg yolk emulsifier 10% 1.1 cal/mL 20% 2 cal/mL 30% 3cal/mL 20% OK for PIV 30% for TNA compounding only! 30-40 % total calories monitor fasting triglycerides contains vitamin K , phosphorus

Fat Emulsion : 

Fat Emulsion 20% product preferred in neonates -10% products contain more phospholipids per gram fat, resulting in decreased lipid clearance, elevated serum triglyceride levels heparin and carnitine supplementation can assist in lipid clearance heparin: 1 unit/mL PN (1000 units/L) carnitine: 8 mg/kg/day

Intravenous Fat Dosage : 

Intravenous Fat Dosage neonates initial: 0.5 gm/kg/day max*: 3-4 gm/kg/day Infants initial: 1 gm/kg/day max*: 2-3 gm/kg/day 8-10% total calories should be provided as fat to prevent EFAD (0.5-1g/kg/day) * Max dose recommendations currently being reevaluated

Fat Emulsions: Cautions : 

Fat Emulsions: Cautions Hyperbilirubinemia -lipids can displace bilirubin from albumin, leading to kernicterus -limit to 1gm/kg/day if on phototherapy Egg protein allergy Hypertriglyceridemia (TG> 200 mg/dL) -infuse over 20-24 hours

Limitations of IV Lipids : 

Limitations of IV Lipids Septicemia -rapid infusion may decrease cellular immunity Thrombocytopenia Fat overload syndrome -neurologic, cardiac, pulmonary, hepatic and renal dysfunction -seen with excess fat administration (>0.17g/kg/hour)

Micronutrients : 

Micronutrients Needs similar to adults Exception: calcium and phosphorus -neonates at greatest risk of osteopenia -keep elemental Ca++: Phos ratio close to 1.7 mg Ca++: 1mg Phos for optimal retention Consider all sources of electrolyte loss or supplementation (drugs/drips/disease state)

Electrolytes : 

Electrolytes Sodium - acetate/chloride/phosphate - preterm: 2-3 mEq/kg/day - infants: 2-4 mEq/kg/day - VLBW require twice as much due to poor renal tubular function - up to 6-8 mEq/kg/day - CHF/total body edema may require less Potassium - serum levels influenced by acid/base balance - preterm: 2-3 mEq/kg/day - infants: 2-4 mEq/kg/day - available as acetate/chloride/phosphate salts Chloride - major role: maintain acid-base balance ***BEWARE OF ORDERS FOR ZERO CHLORIDE****

Minerals : 

Minerals Calcium neonates < 2kg: 3-4.5 mEq/kg/day >2 kg: 2-3 mEq/kg/day Phosphorus neonates < 2kg: 1.5- 1.25 mM/kg/day >2 kg: 1-2 mM/kg/day Magnesium neonates < 2kg: 0.35- 0.6 mEq/kg/day >2 kg: 0.25- 0.5 mEq/kg/day

Trace Elements : 

Trace Elements Important component of metabolic pathways May be increased or removed based on comorbid clinical conditions examples -supplemental zinc for patient with GI losses -removal of Cu/Mn in liver disease -removal of Cr in renal disease

Trace Elements : 

Trace Elements probably not necessary for patients on PN < 1 week exception: premature infants -majority of trace element stores acquired during the 3rd trimester neonatal trace element products contain higher concentrations of zinc, reflecting their increased requirements

Trace Minerals Typically Added to PN : 

Trace Minerals Typically Added to PN Zinc copper chromium manganese selenium Iron iodine

Multivitamins : 

Multivitamins At birth, neonate’s vitamin status reflective of maternal stores Preterm infants have different requirements than full term due to low vitamin status and immature metabolic pathways Commercial products provide both water soluble and fat soluble vitamins based on AMA NAG recommendations Current products not designed for neonates - may need to supplement ELBW infants with vitamin A (5000 IU 3x/week)

Multivitamins : 

Multivitamins DO NOT USE ADULT MVI IN NEONATES!! -adult formulations contain propylene glycol or polysorbate 80 or 20 Special pediatric MVI available - patients < 11 years of age - contains 200 mCg vitamin K/vial - contains more Vitamin D - dose 2 mL/kg, maximum dose 5 mL

Administration of TPN : 

Administration of TPN 24 hour -hospitalized patients -not practical in home patients cyclic -popular with home patients -patient must be tapered on/off solution to avoid hyper/hypoglycemia lipids -separate infusion (12 hr hang time per CDC)

Compounding Problems : 

Compounding Problems

Factors Affecting Ca/Phos Solubility : 

Factors Affecting Ca/Phos Solubility Calcium/phosphate salt concentrations pH of final solution Type/quantity of AA used Temperature Time Magnesium content Order of mixing

Ignore it. Use various rules of thumb.Use compatibility research results. : 

Ignore it. Use various rules of thumb.Use compatibility research results. How do pharmacists protect their parenteral nutrition patients from inadvertent calcium phosphate precipitation?

“MAGIC NUMBER ”If the sum (or product) of the calcium and phosphate do not exceed X, then the PN admixture is OK.Where X = “MAGIC NUMBER ” : 

“MAGIC NUMBER ”If the sum (or product) of the calcium and phosphate do not exceed X, then the PN admixture is OK.Where X = “MAGIC NUMBER ”

Magic Numbers Don’t Work! : 

Magic Numbers Don’t Work!

Factors Affecting Ca/Phos SolubilityExact Predictions Are Not Possible! : 

Factors Affecting Ca/Phos SolubilityExact Predictions Are Not Possible! Calcium/phosphate salt concentrations Type of calcium salt used pH of final solution Type/quantity of AA used Aminosyn pH 5.3 TrophAmine pH 5-6 FreAmine pH 6-7 No protein, can’t add both calcium and phosphorus! Quantity of dextrose used Temperature Time Magnesium content (no AA, can’t add both Mg++ & phos) Order of mixing

Influence of Amino Acid Products on Calcium and Phosphate Compatibility in PN : 

Influence of Amino Acid Products on Calcium and Phosphate Compatibility in PN Trissel LA. Trissel’s™ Calcium and Phosphate Compatibility in Parenteral Nutrition. TriPharma Communications, Houston, TX 2001.

Influence of Amino Acid Products on Calcium and Phosphate Compatibility in PN : 

Influence of Amino Acid Products on Calcium and Phosphate Compatibility in PN Trissel LA. Trissel’s™ Calcium and Phosphate Compatibility in Parenteral Nutrition. TriPharma Communications, Houston, TX 2001.

Calcium-Phosphate Solubilityfactors that IMPROVE stability : 

Calcium-Phosphate Solubilityfactors that IMPROVE stability Addition of phosphorus before calcium Low pH amino acids Final calcium concentration < 10 mEq/L Final phosphorus concentration < 30mEq/L Increased amino acid concentrations Lower final pH Reduced storage temperature (4°C) Use of calcium gluconate or acetate salts

Mechanical Complications of Parenteral Nutrition : 

Mechanical Complications of Parenteral Nutrition CVL related -malposition -pneumo -hemothorax -blockage/thrombosis -embolization infusate related -superficial extravasation -deep extravasation

Infectious Complications of PN Risk Factors : 

Infectious Complications of PN Risk Factors critical illness foreign body in bloodstream mucosal atrophy multiple antibiotics

Metabolic Complications of PN : 

Metabolic Complications of PN azotemia electrolyte imbalances glucose intolerance cholestasis metabolic bone disease urolithiasis coagulopathy, thrombocytopenia

Cholestasis : 

Cholestasis

Cholestasis : 

Cholestasis

Etiology of PN Associated Cholestasis (PNAC) : 

Etiology of PN Associated Cholestasis (PNAC) amino acid imbalances ratio of carbohydrate: fat nutrient deficiencies phytosterols inflammation lack of enteral feeding

Clinical Outcome : 

Clinical Outcome Cholestasis is progressive while on PN Cirrhosis Liver failure Liver transplant or death Often a race between liver failure and bowel adaptation

Etiology : 

Amino acid imbalances Ratio of carbohydrate: fat Nutrient deficiencies Phytosterols Inflammation Etiology

Prevention : 

Prevention Cycling PN Trophic enteral feedings Protection of PN from light

Treatment Options : 

Treatment Options Limit intravenous fat < 1g/kg/day average ? Limit carbohydrate calories Eliminate hepatotoxic medications Absolute: 100% enteral feeds and No PN

Pharmacologic Approaches : 

Pharmacologic Approaches Ursodiol Sincalide Oral antibiotics Cholestyramine Enzyme inducers (phenobarbital/rifampin)

Clinical Experience:Omegaven in the Treatment of PN Associated Liver Disease : 

Clinical Experience:Omegaven in the Treatment of PN Associated Liver Disease Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Pediatrics 2006 118(1):e197-201

Omegaven® : 

Omegaven® Typically used in combination with Intralipid Max dose 0.2g/kg/day (per manufacturer) Not indicated for use in children Not intended to be used as monotherapy Not FDA approved

: 

Comparison of Parenteral Fat Emulsions (10 grams fat/100 mL)

Results: Treatment v. Control : 

Results: Treatment v. Control Gura et al Pediatrics 2008

Aluminum Toxicity : 

Aluminum Toxicity PN associated Al toxicity known since 1980’s Changes in manufacturing methods has decreased Al contamination in comparison to products used in earlier studies FDA mandate to reduce patient exposure to aluminum took effect July 26, 2004

Aluminum Toxicity : 

Aluminum Toxicity associated with impaired bone mineralization, renal insufficiency and neurotoxicity FDA mandate: limit aluminum intake in PN to < 5 mCg/kg/day neonates at greatest risk avoid products with aluminum contamination -? potassium phosphate -? calcium gluconate

What does this mean???? : 

What does this mean???? PN admixtures are complex multi-component systems; each has to be considered independently Pharmacists still need better products for their patients Magic Numbers” don’t work reliably to protect patients against precipitation Calcium and phosphates precipitation is influenced by a multiplicity of factors FDA aluminum mandate will present new challenges to pharmacists in providing safe and effective PN solutions We still have work to do!

Thank you! : 

Thank you!